Effect of chronic renal failure on the hepatic, intestinal, and renal expression of bile acid transporters

Gai, Zhibo and Chu, Lei and Hiller, Christian and Arsenijevic, Denis and Penno, Carlos A. and Montani, Jean-Pierre and Odermatt, Alex and Kullak-Ublick, Gerd A.. (2014) Effect of chronic renal failure on the hepatic, intestinal, and renal expression of bile acid transporters. American Journal of Physiology - Renal Physiology, 306 (1). F130-137.

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Official URL: http://edoc.unibas.ch/50548/

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Although the kidney is believed to play a minor role in bile acid (BA) excretion, chronic renal failure (CRF) has been reported to be associated with increased serum bile acid levels and alterations in BA homeostasis. The mechanisms for elevated BA levels are poorly understood in both clinical and experimental studies. This study was designed to examine the effects of naturally progressing CRF of longer duration on the hepatic and renal mRNA and protein levels of the BA-synthesizing enzyme Cyp7a1 and the BA transporters Ntcp, Bsep, Mrp3, Ost-α, and Ost-β. Sprague-Dawley rats were randomized to the CRF group (⅚ nephrectomy) or to the sham-operated control group and were analyzed 8 wk after surgery. Results obtained in the CRF rats were compared with those obtained in rats that had undergone uninephrectomy (UNX). The CRF group exhibited significantly increased plasma cholesterol and BA concentrations. Hepatic Cyp7a1 mRNA and protein levels were almost identical in the two groups. Hepatic Mrp3, Ost-α, and Ost-β expression was increased, suggesting increased basolateral efflux of bile acids into the blood. However, no such changes in BA transporter expression were observed in the remnant kidney. In UNX rats, similar changes in plasma BA levels and in the expression of BA transporters were found. We hypothesize that the increase in plasma BA is an early event in the progression of CRF and is caused by increased efflux across the basolateral hepatocyte membrane.
Faculties and Departments:05 Faculty of Science > Departement Pharmazeutische Wissenschaften > Pharmazie > Molecular and Systems Toxicology (Odermatt)
UniBasel Contributors:Odermatt, Alex
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:American Physiological Society
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:04 Dec 2017 08:30
Deposited On:04 Dec 2017 08:30

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